title: Visualization of clot lysis in a rat embolic stroke model: application to comparative lytic efficacy.
abstract: OBJECTIVE
  The purpose of this study was to develop a novel MRI method for imaging clot lysis in a rat embolic stroke model and to compare tissue plasminogen activator (tPA)-based clot lysis with and without recombinant Annexin-2 (rA2).
  
  
  METHODS
  In experiment 1 we used in vitro optimization of clot visualization using multiple MRI contrast agents in concentrations ranging from 5 to 50 μL in 250 μL blood. In experiment 2, we used in vivo characterization of the time course of clot lysis using the clot developed in the previous experiment. Diffusion, perfusion, angiography, and T1-weighted MRI for clot imaging were conducted before and during treatment with vehicle (n=6), tPA (n=8), or rA2 plus tPA (n=8) at multiple time points. Brains were removed for ex vivo clot localization.
  
  
  RESULTS
  Clots created with 25 μL Magnevist were the most stable and provided the highest contrast-to-noise ratio. In the vehicle group, clot length as assessed by T1-weighted imaging correlated with histology (r=0.93). Clot length and cerebral blood flow-derived ischemic lesion volume were significantly smaller than vehicle at 15 minutes after treatment initiation in the rA2 plus tPA group, whereas in the tPA group no significant reduction from vehicle was observed until 30 minutes after treatment initiation. The rA2 plus tPA group had a significantly shorter clot length than the tPA group at 60 and 90 minutes after treatment initiation and significantly smaller cerebral blood flow deficit than the tPA group at 90 minutes after treatment initiation.
  
  
  CONCLUSIONS
  We introduce a novel MRI-based clot imaging method for in vivo monitoring of clot lysis. Lytic efficacy of tPA was enhanced by rA2.
authors.affiliation: Department of Neurology, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Ronn P
authors.initials: RP
authors.lastname: Walvick
authors.forename: Bernt T
authors.initials: BT
authors.lastname: Bråtane
authors.forename: Nils
authors.initials: N
authors.lastname: Henninger
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Sicard
authors.forename: James
authors.initials: J
authors.lastname: Bouley
authors.forename: Zhanyang
authors.initials: Z
authors.lastname: Yu
authors.forename: Eng
authors.initials: E
authors.lastname: Lo
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Wang
authors.forename: Marc
authors.initials: M
authors.lastname: Fisher
mesh_terms: D000818:Animals; D017306:Annexin A2 / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005337:Fibrin / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D020766:Intracranial Embolism / Q000097:blood / Q000188:drug therapy*; D020767:Intracranial Thrombosis / Q000097:blood / Q000188:drug therapy*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D015912:Thrombolytic Therapy / Q000379:methods
chemical_list: D017306:Annexin A2; D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D005337:Fibrin; D005340:Fibrinogen